Congenital osteopetrosis is a rare osteosclerotic bone disease characterized by both a defect in osteoclastic function and reduced generation of superoxide by leukocytes. The disease is frequently fatal during the first decade of life. A six-month trial of therapy with recombinant human interferon gamma-1b in eight patients with osteopetrosis provided evidence of benefit, prompting this study of more prolonged therapy.

We studied 14 patients with severe osteopetrosis treated with subcutaneous injections of recombinant human interferon gamma-1b (1.5 μg per kilogram of body weight per dose) three times per week for at least 6 months; 11 patients were treated for 18 months. We assessed the effect of therapy by evaluating the patients' clinical status, measuring blood counts and biochemical markers of bone turnover, and performing bone marrow imaging and bone biopsies.

After 6 months of therapy, all 14 patients had decreases in trabecular-bone area (determined by histomorphometric analysis of bone-biopsy specimens) and increases in bone marrow space (determined by marrow imaging), and the improvement was sustained in the 11 patients treated for 18 months. The mean (±SD) hemoglobin concentration increased from 7.5±2.9 to 10.5±0.3 g per deciliter (P = 0.05), and superoxide generation by granulocyte–macrophage colonies increased (P<0.001) after 18 months of therapy. In six patients for whom pretreatment data were available, there was a 96 percent decrease in the frequency of infections requiring antibiotic therapy during interferon treatment. There were no side effects necessitating the discontinuation of therapy.

Long-term therapy with interferon gamma in patients with osteopetrosis increases bone resorption and hematopoiesis and improves leukocyte function.